Hypertrophic cardiomyopathy and fabry disease: right ventricular to pulmonary artery coupling can differentiate both?

Background

Right ventricular (RV) adaptation to pulmonary arterial (PA) load—expressed through RV-to-PA coupling—has emerged as a sensitive marker of early RV dysfunction across various cardiac diseases. Hypertrophic cardiomyopathy (HCM) and Fabry disease (FD) can both present with left ventricular hypertrophy and overlapping clinical features, often complicating differential diagnosis. Evaluating RV–PA coupling may therefore provide an additional functional parameter to help differentiate Fabry disease from HCM.

Purpose

To assess whether RV–PA coupling indices — TAPSE/PASP (Tricuspid Annular Plane Systolic Excursion/Pulmonary Artery Systolic Pressure), FAC/PASP (Fractional Area Change), and RV-FWS/PASP (Right Ventricular Free Wall Strain) — have diagnostic value in distinguishing hypertrophic cardiomyopathy from Fabry disease.

Methods

Retrospective study that included HCM (n=30) and FD (n=30) patients evaluated between 2014 and 2021. RV structure and function were analyzed by two blinded observers using echocardiography and 2D-STE. Diagnostic performance of the TAPSE/PASP, FAC/PASP, and RV-GLS/PASP ratios was examined using receiver operating characteristic (ROC) analysis, with DeLong’s test applied for comparison of AUCs.

Results

FD patients had a median age of 64.6±10.7 years and NT-proBNP levels of 899±1016pg/ml. HCM patients has a median age of 59.8±13.6 years and NT-proBNP levels of 1117±1103pg/ml. Septal wall thickness was significanty higher in HCM (18.7±2.25 vs 17.6±2.7mm, p=0.047). RV–PA coupling indices were not significantly different between FD and HCM, including TAPSE/PASP ratio (0.871±0.253 vs 0.754±0.219, p=0.061), FAC/PASP ratio (1.608±0.435 vs 1.420±0.367, p=0.078) and RV-FWS/PASP ratio (0.507±0.171 vs 0.434±0.143, p=0.074).

In ROC curve analysis, TAPSE/PASP ratio had an area under the curve (AUC) of 0.632 [0.498–0.753] (p=0.070). FAC/PASP ratio showed an AUC of 0.631 [0.496–0.752] (p=0.073). The RV-FWS/PASP ratio had an AUC of 0.643 [0.509-0.762] (p=0.049) with an associated cutoff of >0.393 for identifying ATTR-CM (sensitivity: 83%; specificity: 47%). Pairwise comparisons showed no significant difference between TAPSE/PASP, FAC/PASP or RV-FWS/PASP ratios in distinguishing FD from HCM. When compared to the RV function parameters not normalized to load, the AUC for RV-FWS was numerically lower than that of the load-normalized parameters (AUC of 0.636 for TAPSE, AUC of 0.685 for FAC and AUC of 0.533 for RV-FWS).

Conclusion

Although the RV-FWS/PASP ratio reached borderline statistical significance in ROC analysis, its low specificity and overall modest AUC limit its clinical usefulness. Taken together, these results suggest that RV–PA coupling, while physiologically relevant, offers only limited diagnostic value for distinguishing FD from HCM in routine practice. Larger studies with more advanced imaging parameters may be needed to clarify whether subtle RV functional signatures can aid in this differential diagnosis.